In the last 20–30 years there has been a dramatic escalation in the prevalence of allergic diseases in industrialized countries. The aetiology of this rise is not known.
Previously, the hygiene hypothesis has proposed that the absence of or reduction in infectious diseases might be a factor for the increase in the prevalence of allergies in industrialized societies. However, this is only one aspect of the multifactorial changes in immune stimuli that have occurred in the past few decades.
In support of a potential role for parasitic helminths in the rise in allergies, an association between infection with helminth parasites and a lower allergic phenotype has been observed in human infections in societies in which helminths are prevalent. Mechanistically, a potential role for helminth-induced IL-10 expression has been implicated in this inverse association.
In experimental animal models, helminths can modulate allergic responses, including anaphylaxis, allergen-induced eosinophilia and compromised lung function. Potential immunological mechanisms postulated for these responses include regulatory T cells and the expression of the regulatory cytokine IL-10 from various cell sources.
We propose that helminths induce a modified pulmonary type 2 response that suppresses inflammation in the lungs. Helminths might have evolved this mechanism of suppression of lung inflammation to prevent death of the host that is due to pulmonary pathology as new infecting larvae migrate through the lungs.
Future research unifying key data from humans infected with helminths or experimental animal infections will identify common mechanisms of suppression of allergies in infection. Understanding these mechanisms will lead to new therapeutic strategies for the treatment of allergic diseases.
There is no immunological mechanism to adequately explain the sudden epidemic in allergies noted in the last 30 years in developed countries. The reduction in the development of allergic disorders observed in individuals infected with parasitic helminths, however, supports a possible role for worms in suppressing allergies. Helminths regulate the immunity of the host to ensure a mutually beneficial environment for the survival of both the parasite and the host. This interplay between helminths and allergic responses raises fundamental questions in immunobiology. Harnessing current mechanistic studies for translational research into helminth infections and atopy might have potential for the identification of novel biomarkers, and even therapeutics, in allergic diseases.
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The authors are currently supported by the Irish Higher Education Authority Programme for Research in Third Level Institutions, with previous support from SFI and The Wellcome Trust.
The authors declare no competing financial interests.
An antigenic substance that can induce an allergic response.
A drug that is used to kill parasitic helminths.
A parasitic helminth in which part of the life cycle involves living in the soil.
A phylum of worms with elongated bodies that include free-living species (such as Caenorhabditis elegans) and parasitic species.
- Filarial worm
A parasitic nematode, the life cycle of which involves an invertebrate intermediate host and a vertebrate primary host.
A class of parasitic flatworms that is often referred to as the flukes, and includes schistosome species in the blood.
A localized cell infiltration surrounding, in this context, a schistosome egg trapped in various tissues. The schistosome egg granuloma comprises a type 2 infiltrate that is rich in TH2 cells, eosinophils and macrophages, which progresses to a fibrotic lesion.
Infective free-swimming larvae of trematodes. Humans are infected when the cercariae penetrate the skin while the individual is in contaminated water.
- Airway hyperresponsiveness
A hyperreactivity of the airways, initiated by exposure to a defined stimulus that is usually tolerated by normal individuals, that causes bronchoconstriction and inflammatory-cell infiltration in allergic individuals.
- Airway remodelling
Chronic changes in the airway architecture of the lungs of allergic individuals that contribute to airway hyperresponsiveness.
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Fallon, P., Mangan, N. Suppression of TH2-type allergic reactions by helminth infection. Nat Rev Immunol 7, 220–230 (2007). https://doi.org/10.1038/nri2039
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Changes in protein expression after treatment with Ancylostoma caninum excretory/secretory products in a mouse model of colitis
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